Animal fetuses may be used for the regeneration of human organs. We have previously generated a transgenic mouse model that allows diphtheria toxin (DT)-induced ablation of Six2-positive nephron progenitor cells (NPCs). Elimination of existing native host NPCs enables their replacement with donor NPCs, which can generate neo-nephrons. However, this system cannot be applied to human NPCs, because DT induces apoptosis in human cells. Therefore, the present study presents a transgenic mouse model for the ablation of NPCs using tamoxifen, which does not affect human cells. Using this system, we successfully regenerate interspecies neo-nephrons, which exhibit urine-producing abilities, from transplanted rat NPCs in a mouse host. Transplantation of human induced pluripotent stem cell (iPSC)-derived NPCs results in differentiation into renal vesicles, which connect to the ureteric bud of the host. Thus, we demonstrate the possibility of the regeneration of human kidneys derived from human iPSC-derived NPCs via NPC replacement.

动物胎儿可用于人体器官的再生。我们先前已经生成了转基因小鼠模型，该模型允许白喉毒素（DT）诱导消融Six2阳性肾单位祖细胞（NPC）。消除现有的本地宿主NPC可以将其替换为供体NPC，后者可以产生新肾单位。然而，该系统不能应用于人的NPC，因为DT诱导人细胞的凋亡。因此，本研究提出了使用他莫昔芬消融NPC的转基因小鼠模型，该模型不影响人类细胞。使用该系统，我们成功地从小鼠宿主中移植的大鼠NPC再生了具有尿液产生能力的种间新肾。人诱导多能干细胞（iPSC）衍生的NPC的移植导致分化为肾小泡，连接到宿主的输尿管芽。因此，我们证明了通过NPC替代从人iPSC衍生的NPC衍生出人肾脏的可能性。